Preliminary results have indicated that there is a lower mean value for sodium pump activity in erythrocytes from subjects who have a history of bipolar manic-depressive psychosis, as compared with controls. In order to determine whether this difference is specific for bipolar affective disorder, erythrocyte Na ion pump activity will be measured in subjects with unipolar depressive psychosis, other depressive disorders, schizoaffective disorder and schizophrenia. Individual fluctuations in Na ion pump activity will be measured in a selected group of patients and controls in longitudinal studies over the course of five years. If the difference proves to be specific for bipolar affective disorder, the possibility of developing a diagnostic test based on the observation will be explored. The characteristics of the erythrocyte membrane sodium plus potassium-dependent adenosinetriphosphatase (NaK-ATPase) will be studied in bipolar affective disorder and an attempt will be made to determine whether a genetic variant is involved in the disorder. The effects of chronic administration of lithium salts on the levels of NaK-ATPase in rat and mouse brain will be determined. Phospholipid levels and phospholipid metabolism in erythrocyte membranes from subjects with the various functional psychoses will be studied. Particular objectives are: to determine the relationship of phosphatidylserine levels to Na ion pump activity in erythrocytes in bipolar manic-depressive psychosis; to determine phosphatidylserine levels and the relative proportions of phosphatidylcholine and phosphatidylethanolamine in erythrocyte membranes in schizophrenia; and to study the metabolism of phosphatidic acid and polyphosphoinositides in erythrocyte membranes in the different functional psychoses.